This guide summarizes the effectiveness and safety of various treatments for preventing fractures among postmenopausal women with osteoporosis. It focuses on postmenopausal women because most of the clinical trials of treatment were conducted in this population. This guide does not examine the effect of treatments on intermediate outcomes, such as bone mineral density or markers of bone turnover. Treatments reviewed include bisphosphonates, selective estrogen receptor modulators (SERMs), hormonal medications, calcium, and vitamin D. The dose and price of drugs reviewed are listed.

Clinical Issue

Osteoporosis increases bone fragility and susceptibility to fracture. It occurs in aging individuals of both sexes but is more common in postmenopausal women. It also can result from secondary causes, such as treatment with glucocorticoids. Each year in the United States, about 1.5 million people experience a fracture related to osteoporosis. Of those with hip fractures, one in five die, and the same number end up in a nursing home within a year of the fracture.

The goal of treating osteoporosis is to prevent fractures and their associated disability. Candidates for treatment include individuals at high risk for fracture as defined by low bone density, history of prior fracture, significant secondary causes for developing osteoporosis, and risk factors for falls, such as difficulty with walking or balance. Selecting treatment requires careful consideration of the benefits, risks, and costs as well as the likelihood of adherence.

Clinical Bottom Line

• Some bisphosphonates (alendronate, risedronate, and zoledronic acid) and estrogen prevent hip and other nonvertebral fractures.
  LEVEL OF CONFIDENCE:
• Raloxifene, estrogen, teriparatide, and most bisphosphonates (alendronate, etidronate, ibandronate, risedronate, and zoledronic acid) prevent vertebral fractures.
  LEVEL OF CONFIDENCE:
• Calcitonin also prevents vertebral fractures.
  LEVEL OF CONFIDENCE:
• Raloxifene, tamoxifen, and estrogen increase the risk of thromboembolic events.
  LEVEL OF CONFIDENCE:
• It is unknown whether bisphosphonates work better to prevent fractures than any other osteoporosis treatments.

Treatment Approaches

Bone Mineral Density

The clinical definition of osteoporosis is based either on evidence of fracture or on the densitometric measurement of bone, bone mineral density (BMD). The most common BMD test is a DXA (dual-energy x-ray absorptiometry). BMD measurements are interpreted according to the number of standard deviations from the mean of a reference population of young adults. This is referred to as the T-score.

A negative value indicates a BMD measurement below the mean. A T-score lower than −2.5 is diagnostic of osteoporosis. If a postmenopausal woman has had a nontraumatic fracture (fragility fracture), she is considered to have osteoporosis regardless of her T-score.

Used with permission from the International Osteoporosis Foundation.

Possible Harms of Treatment

Selecting a Treatment Approach

Most of these drugs prevent fractures among postmenopausal women with osteoporosis. When selecting a treatment, consider these other factors.

Consider barriers to adherence and persistence, including mode of administration, dosing regimens, and cost.

• Weekly users of bisphosphonates have higher rates of adherence and persistence compared with daily users.
• Cost may be a barrier. Generics are not widely available. Intravenous drugs incur additional expense. Drugs, doses, and prices are listed in the Treatments for Osteoporosis by Dose, Administration Route, and Price table.. The Partnership for Prescription Assistance can also provide information on public and private assistance programs. Web site: www.pparx.org. Phone: (800) 477-2669.

Table

Treatments for Osteoporosis by Dose, Administration Route, and Price.

Consider the risk of adverse events.

• GI problems can occur with oral bisphosphonates. Women who experience symptoms such as reflux or nausea may need to switch medications.
• Women with a history of serious GI disease, such as GI bleeds, should avoid bisphosphonates, except zoledronic acid.
• Avoid zoledronic acid for women at high risk for atrial fibrillation.

Consider supplementation.

• Adequate calcium and vitamin D intake is needed for normal bone homeostasis. Encourage women to take calcium supplements in divided doses and get adequate vitamin D.

Adherence

Treatment to prevent fractures is usually long term. Consider how well the woman will be able to take the medication as prescribed (adherence) and the possible barriers to continuing treatment (persistence).

• Rates of adherence and persistence with alendronate, etidronate, risedronate, raloxifene, estrogen, calcitonin, calcium, and vitamin D are low in women with osteoporosis.
  LEVEL OF CONFIDENCE:
• Factors that affect adherence and persistence include side effects, absence of disease-related symptoms, comorbid conditions, ethnicity, socioeconomic status, and dosing regimens.
  LEVEL OF CONFIDENCE:

Still Unknown

• There is no research comparing exercise with other treatments for fracture prevention.
• We do not have enough data to determine if one class of drugs is superior to another for fracture prevention.
• We do not have enough data to determine if any of the bisphosphonates are more effective than the others for fracture prevention.

Resource for Patients

Osteoporosis Treatments That Help Prevent Broken Bones: A Guide for Women After Menopause is a companion to this Clinician’s Guide. It can help women talk with their health care professional about treatment options. It provides information about the effectiveness of osteoporosis treatments for preventing fractures, side effects, and costs.

For More Information

For electronic copies of the consumer’s guide, this clinician’s guide, and the full systematic review, visit this Web site: www.effectivehealthcare.ahrq.gov

For free print copies call: The AHRQ Publications Clearinghouse, (800) 358–9295

Consumer’s Guide, AHRQ Pub. No. 08-EHC008-2A

Clinician’s Guide, AHRQ Pub. No. 08-EHC008-3

For current osteoporosis screening recommendations, visit the U.S. Preventive Services Task Force Web site: www.ahrq.gov/clinic/uspstf/uspsoste.htm

Source

The source material for this guide is a systematic review of 101 research publications about efficacy and 490 research publications about adverse events. The review, Comparative Effectiveness of Treatments to Prevent Fractures in Men and Women With Low Bone Density or Osteoporosis (2007), was prepared by the Southern California Evidence-based Practice Center at RAND. The Agency for Healthcare Research and Quality (AHRQ) funded the systematic review and this guide. The guide was developed using feedback from clinicians who reviewed preliminary drafts.

AHRQ created the John M. Eisenberg Center at Oregon Health & Science University to make research useful for decisionmakers. This guide was prepared by David Hickam, M.D., Bruin Rugge, M.D., Theresa Bianco, Pharm. D., Sandra Robinson, M.S.P.H., Erin Davis, B.A., Martha Schechtel, R.N., and Valerie King, M.D., of the Eisenberg Center.